Overview of the process followed to estimate the maximum potential market sized for HIVDR testing in LMIC (use case 1).

PLHIV: people living with HIV. ART: antiretroviral therapy. DTG: dolutegravir. CHAI: Clinton Health Access Initiative. EAC: enhanced adherence counselling.</p

Commercially available next-generation sequencing HIV drug resistance assays.

Commercially available next-generation sequencing HIV drug resistance assays.</p

High-level timeline of the development and availability of HIV drug resistance tests.

OLA: Oligonucleotide ligation assay. PANDAA: Pan-Degenerate Amplification and Adaptation. RUO: research use only. FDA: Food and Drug Administration. CE: conformité européenne.</p

Commercially available bulk/Sanger-based sequencing assays.

Commercially available bulk/Sanger-based sequencing assays.</p

Maximum market size for use case 1 (DTG failures).

Maximum market size for use case 1 (DTG failures).</p

Potential commercially available point of care HIV drug resistance assays.

Potential commercially available point of care HIV drug resistance assays.</p

Maximum market size for use case 2 (PI/r failures).

Maximum market size for use case 2 (PI/r failures).</p

Cohorts without physical tracing.^*.

*<p>Defined as physical tracing to the patient’s place of residence and was available to at least half the study population. Note that 7 cohorts <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056047#pone.0056047-Tassie1" target="_blank">[17]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056047#pone.0056047-Bisson1" target="_blank">[32]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056047#pone.0056047-Chung1" target="_blank">[36]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056047#pone.0056047-Wester1" target="_blank">[48]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056047#pone.0056047-Chinh1" target="_blank">[52]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056047#pone.0056047-Sharma1" target="_blank">[62]</a> reported phone only tracing was available to a proportion of the study population, and 4 cohorts <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056047#pone.0056047-Charalambous1" target="_blank">[34]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056047#pone.0056047-Toure1" target="_blank">[47]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056047#pone.0056047-Balestre1" target="_blank">[54]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056047#pone.0056047-Hong1" target="_blank">[58]</a> reported physical tracing for a minority of the study population ^&amp; All ART naïve at baseline unless stated.</p>#<p>Sample size determined via contact with study authors.</p>̂<p>Benin, Cote d’Ivoire, Gambia, Mali, Nigeria, Senegal.</p>+<p>Lesotho, Mozambique, Tanzania, Zimbabwe <b>Notes:</b> ART, antiretroviral therapy; WHO, World Health Organization; LTFU, lost to follow up; TF, transfer; NR, not reported; F/U, follow up; NGO, non-governmental organization; NNRTI. Non-nucleoside reverse transcriptase inhibitors; PI, protease inhibitors; NRTI, nucleoside reverse transcriptase inhibitors.</p

Cohorts with physical tracing.^*.

*<p>Defined as physical tracing to the patients place of residence and was available to at least half the study population.</p>&amp;<p>All ART naïve at baseline unless stated <b>Notes:</b> ART, antiretroviral therapy; WHO, World Health Organization; LTFU, lost to follow up; TF, transfer; NR, not reported; F/U, follow up; NGO, non-governmental organization; NNRTI. Non-nucleoside reverse transcriptase inhibitors; PI, protease inhibitors; NRTI, nucleoside reverse transcriptase inhibitors;</p

Effects of Physical Tracing on Estimates of Loss to Follow-Up, Mortality and Retention in Low and Middle Income Country Antiretroviral Therapy Programs: A Systematic Review

<div><h3>Background</h3><p>A large proportion of patients receiving antiretroviral therapy (ART) in low and middle income countries (LMICs) have unknown treatment outcomes and are classified as lost to follow-up (LTFU). Physical tracing of patients classified as LTFU is common; however, effects of tracing on outcomes remains unclear. The objective of this systematic review is to compare estimates of LTFU, mortality and retention in LMIC in cohorts of patients with and without physical tracing.</p> <h3>Methods and Findings</h3><p>We systematically identified studies in LMIC programmatic settings using MEDLINE (2003–2011) and HIV conference abstracts (2009–2011). Studies reporting the proportion LTFU 12-months after ART initiation were included. Tracing activities were determined from manuscripts or by contacting study authors. Studies were classified as “tracing studies” if physical tracing was available for the majority of patients. Summary estimates from the 2 groups of studies (tracing and non-tracing) for LTFU, mortality, stop of ART, transfers out, and retention on ART were determined. 261 papers and 616 abstracts were identified of which 39 studies comprising 54 separate cohorts (n = 187,666) met inclusion criteria. Of those, physical tracing was available for 46% of cohorts. Treatment programs with physical tracing activities had lower estimated LTFU (7.6% vs. 15.1%; p&lt;.001), higher estimated mortality (10.5% vs. 6.6%; p = .006), higher retention on ART (80.0 vs. 75.8%; p = .04) and higher retention at the original site (80.0% vs. 72.9%; p = .02).</p> <h3>Conclusions</h3><p>Knowledge of patient tracing is critical when interpreting program outcomes of LTFU, mortality and retention. The reduction of the proportion LTFU in tracing studies was only partially explained by re-classification of unknown outcomes. These data suggest that tracing may lead to increased re-engagement of patients in care, rather than just improved classification of unknown outcomes.</p> </div